Pain can be defined as an unpleasant sensation ranging from mild discomfort to agonizing distress, associated with real or potential tissue damage, or a disorder of the nervous system. Pain is a response to impulses from the peripheral nerves in damaged tissue, which pass to nerves in the spinal cord. All animals experience some degree of pain during life, whether through injury or disease. As such, one of the major areas of drug research is the development of analgesics to be used in pain management.
One area in which pain is more frequently experienced than in others is inflammation. Pain associated with inflammation can be caused by pathologic processes in somatic structures or viscera or by prolonged dysfunction of parts the peripheral nervous system. Pain associated with inflammation may be the result of recurrent injuries, trauma, headache, arthritis including osteoarthritis, chronic obstructive pulmonary disease, psoriasis, or other pathologies. Pain associated with inflammation may be acute or chronic depending on the duration, level and extent of the inflammation.
Irrespective of the type or cause of pain it is important that early treatment is obtained as unrelieved pain can have profound psychological effects on the patient and acute pain which is poorly managed initially can degenerate into chronic pain which may prove more difficult to treat. However, the difficulty is that pain perception is a complex psychophysical process that can be modified by attitude, attention and suggestion. No other sensation depends as much on cognition and information processing as does pain. See, for example, Kling, J. W. and Riggs, L. A., Editors, Woodworth & Schlosberg's Experimental Psychology, 3rd. edition, Holt, Rinehart and Winston, Inc., New York, N.Y. (1971).
Therapeutic management of pain includes four steps:                1) peripheral level pain is treated with ice packs, heat pads, massage or non-steroidal anti-inflammatory drugs (NSAIDs) like aspirin or ibuprofen to inhibit local responses to trauma and prevent stimulation of nociceptors;        2) mild pain is treated with non-opioid analgesics such as paracetamol;        3) moderate or persisting pain is treated with a weak opioid like dihydrocodein plus non-opioid analgesics; and        4) severe pain that persists or increases is treated with a potent opioid eg nalbuphine plus non-opioid analgesic.        
Despite all of the recent advances in the treatment of pain and/or inflammation, the majority of the agents used have side effects or limitations. For example, aspirin can cause irreversible inhibition of platelet function and cause gastric irritation. It can precipitate hypersensitivity reactions including asthma, and there may be cross sensitivity with other NSAIDs. It also interacts with a number of other drugs and is especially hazardous with warfarin.
Paracetamol does not have the haematological or GI adverse effects associated with aspirin and side effects are rare; however, overdosage is particularly dangerous as it may cause severe or sometimes fatal hepatic damage.
Mild NSAIDs such as ibuprofen have weaker anti-inflammatory properties than aspirin, but a much lower risk of GI side effects than aspirin and other NSAIDs.
Dihydrocodeine is a weak opioid which is effective for the relief of moderate pain of visceral origin. However, it is known to cause nausea, vomiting and constipation.
Co-dydramol and co-codamol are compound analgesic preparations which combine paracetamol with a low dose of an opioid analgesic eg. dihydrocodeine or codeine.
NSAIDs used regularly in full dosage have a lasting analgesic and anti-inflammatory effect which makes them particularly useful for treatment of continuous regular pain associated with inflammation, musculoskeletal and soft tissue disorders.
Diclofenac combines good efficacy with relatively low incidence of side effects. It is stronger than ibuprofen but has more side effects than ibuprofen. It is associated with intermediate risk of serious upper gastro-intestinal side effects.
As can be seen, many of currently used analgesics have associated side effects include dyspepsia, gastric or small bowel bleeding, ulceration, renal insufficiency, confusion, rash, headache, hepatic toxicity. NSAIDs also reversibly inhibit platelet aggregation and prolong bleeding time. Therefore, the use of analgesic compositions must be considered within the treatment context. At the same time, the treatment context is a factor that must be taken into account when considering the pharmacology and physiology of analgesic ingredients.
There is thus a continued need for new analgesics that can provide fast and reliable analgesia and preferably also anti-inflammatory benefits.